Condition category
Nutritional, Metabolic, Endocrine
Date applied
24/10/2017
Date assigned
25/10/2017
Last edited
24/10/2017
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Not yet recruiting

Plain English Summary

Background and study aims
Reduced awareness of low blood glucose (hypoglycaemia) affects about 25-30% of all people with type 1 diabetes. It puts that person at a much greater risk of severe hypoglycaemia with loss of consciousness or coma and it remains one of the major concerns of people with type 1 diabetes. There are currently no treatments for this condition other than structured education and sometimes pancreas transplantation when problems become extreme. This study is based on the new idea that repeated mild to moderate episodes of low glucose build up a memory in your brain which then learns to adapts to it. The brain has to adapt because each time it experiences low glucose the cells in the body become very stressed and this is damaging in the long term. This type of memory is called ‘habituation’ and this raises the possibility that by introducing a new stress, ‘dishabituation’, it might be possible to restore hypoglycaemia awareness. This study uses short bursts of high intensity exercise as a dishabituating stimulus to see if this will improve a person's awareness of low blood glucose.

Who can participate?
Patients aged 18 to 55 with type 1 diabetes who have an impaired awareness of hypoglycaemia

What does the study involve?
Participants are randomly allocated to either a period of rest or a high intensity exercise program on an exercise bike. The following day they undergo a hypoglycaemic clamp study where their blood glucose level is reduced in a controlled manner and their response is monitored using blood tests and questionnaires. Participants cross over two weeks later to undergo the opposite intervention and again undergo a hypoglycaemic clamp study. There are 5-7 visits to the Clinical Research Centre, and the study lasts about 6 weeks in total.

What are the possible benefits and risks of participating?
Exercise is recommended for all people with type 1 diabetes for a variety of health benefits. It is hoped that this type of exercise may help participants regain symptoms of low blood glucose, and also that they will feel the general benefits and improvement in well-being with exercise. In addition, participants see a diabetes doctor at every visit and are given guidelines and advice as to how to adjust their insulin so that they can exercise more confidently. The study may not immediately benefit participants, but if the results of the study are positive this may lead on to further research in this area and change the practice of managing patients with diabetes who have lost the symptoms and warning signs of hypoglycaemia. If so, participants may gain eventually from our discovering a new treatment for their condition. Exercise can increase the risk of hypoglycaemia, both during the activity and afterward during the night. Participants are supervised and have their glucose monitored regularly throughout the exercise program via continuous glucose monitor and are given standard advice about insulin adjustments before and after exercise. In addition, all participants are fitted with a continuous glucose monitor before, during and after the study. During exercise participants are fitted with a heart rate monitor. The hypoglycaemic clamp technique is very safe and is accepted as the gold standard worldwide for the study of hypoglycaemia. The chief investigator and his laboratory have experience in its use and have published in this area. It is a well-established, safe research technique with no major reported side effects. Participants have their blood glucose monitored every 5 minutes, and heart rate and blood pressure are monitored throughout. Blood sampling may cause some mild brief pain and bruising. As always care is taken by the doctor to minimise distress. There is a maximum of 7 visits to the Clinical Research Centre during this study. The researchers have attempted to reduce this burden by making 2 visits optional by teaching participants how to fit the continuous glucose monitor so that they can do this themselves rather than attend the Clinical Research Centre. They provide transport (taxi) or car parking for all of these visits.

Where is the study run from?
Ninewells Hospital (UK)

When is the study starting and how long is it expected to run for?
August 2017 to August 2019

Who is funding the study?
1. Juvenile Diabetes Research Foundation International
2. Diabetes UK

Who is the main contact?
Prof. Rory McCrimmon

Trial website

Contact information

Type

Scientific

Primary contact

Prof Rory McCrimmon

ORCID ID

Contact details

School of Medicine
Ninewells Hospital and Medical School
Ninewells Avenue
Dundee
DD2 9SY
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

2017DM15

Study information

Scientific title

Dishabituation as a treatment for impaired awareness of hypoglycaemia in type 1 diabetes: a randomised cross over study

Acronym

Study hypothesis

People with type 1 diabetes 'habituate' to hypoglycaemia and this leads to the development of impaired awareness of hypoglycaemia. Therefore the counter regulatory response to hypoglycaemia and hypoglycaemia awareness in people with type 1 diabetes can be restored through the introduction of a novel strong dishabituating stimulus.

Ethics approval

East of Scotland Regional Research Ethics Committee - approval pending

Study design

Randomised cross over study

Primary study design

Interventional

Secondary study design

Randomised cross over trial

Trial setting

Hospitals

Trial type

Other

Patient information sheet

Not available in web format, please use the contact details to request a patient information sheet

Condition

Type 1 diabetes

Intervention

Participants will be randomised to start with a period of rest or a high intensity exercise program on an exercise bike. The following day they will undergo a hypoglycaemic clamp study where their blood glucose level will be reduced in a controlled manner and their response monitored in the form of blood tests and questionnaires. Participants will cross over two weeks later to undergo the opposite intervention and again undergo a hypoglycaemic clamp study. There will be 5-7 visits to the Clinical Research Centre, the study will last approximately 6 weeks in total.

Intervention type

Behavioural

Phase

Drug names

Primary outcome measures

The difference in the adrenaline response to hypoglycaemia following the HIT and no exercise protocols, measured at baseline, immediately post HIT intervention and -30, 0, 30, 60 and 90 minutes into hypoglycaemic clamp

Secondary outcome measures

1. Changes in awareness of hypoglycaemia and symptom scores (Edinburgh Hypoglycaemia Score), measured at baseline, immediately post intervention and -30, 0, 30, 60 and 90 minutes ± 10 minutes into hypoglycaemic clamp
2. Changes in cognitive function (Digital Symbol Substitution Test, 4-Choice Reaction Time), measured at baseline, immediately post intervention and -30, 0, 30, 60 and 90 minutes ± 10 minutes into hypoglycaemic clamp
3. Changes in mood (standard validated psychometric measures of mood state), measured at baseline, immediately post intervention and -30, 0, 30, 60 and 90 minutes ± 10 minutes into hypoglycaemic clamp
4. Changes in other counter regulatory hormones (glucagon, noradrenaline, lactate, cortisol, growth hormone, insulin, cytokine panel and brain derived neurotrophic factor), measured at baseline both interventions, immediately post HIT intervention and -30, 0, 30, 60 and 90 minutes ± 10 minutes into hypoglycaemic clamp (insulin will only be measured during hypoglycaemic clamp study)

Overall trial start date

02/08/2017

Overall trial end date

02/08/2019

Reason abandoned

Eligibility

Participant inclusion criteria

1. Adults ≥18 and ≤ 55 years
2. Type 1 diabetes
3. > 5 years disease duration
4. HbA1c < 75 mmol/l
5. On intensive insulin therapy (CSII or MDI)
6. Impaired awareness of hypoglycaemia (Gold score ≥4 or Modified Clark score≥4 or DAFNE hypoglycaemia awareness rating 2 or 3)

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

12

Participant exclusion criteria

1. Competitive sportsman/woman
2. History of significant heart disease
3. Treatment with beta blockers
4. Renal impairment (eGFR<60)
5. History of significant lung disease – that limits exercise
6. History of significant neurological disease – including seizures second to hypoglycaemia
7. High risk foot disease
8. Previous amputation of toes/foot/leg
9. Pregnant women or breast feeding mothers
10. Participation in HIT or equivalent in past 6 months
11. Physical ability that may limit exercise
12. Inability to give consent

Recruitment start date

08/01/2018

Recruitment end date

01/08/2018

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Clinical Research Centre Ninewells Hospital University of Dundee
James Arnott Drive Ninewells Hospital and Medical School
Dundee
DD2 1GZ
United Kingdom

Sponsor information

Organisation

University of Dundee/NHS Tayside

Sponsor details

Tayside Medical Sciences Centre (TASC)
Level 3
George Pirie Way
Ninewells Hospital
Dundee
DD2 9SY
United Kingdom

Sponsor type

Other

Website

Funders

Funder type

Charity

Funder name

Juvenile Diabetes Research Foundation International

Alternative name(s)

Juvenile Diabetes Research Foundation, International, JDRF

Funding Body Type

private sector organisation

Funding Body Subtype

foundation

Location

United States of America

Funder name

Diabetes UK

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Results and Publications

Publication and dissemination plan

As this is a non-CTIMP single intervention a detailed protocol will be published with the final manuscript. The trialists will publish the results of this study in a medical journal as well as to present at national and international conferences. In addition, they will also disseminate the results through meetings with various stakeholder groups as well as communicate through other media options.

IPD sharing statement
The data sharing plans for the current study are unknown and will be made available at a later date.

Intention to publish date

01/08/2020

Participant level data

To be made available at a later date

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes